It has been demonstrated that CD8 positive CTLs recognize epitope peptides derived from the tumor-associated antigens (TAAs) found on major histocompatibility complex (MHC) class I molecule, and then kill the tumor cells. Since the discovery of the melanoma antigen (MAGE) family as the first example of TAAs, many other TAAs have been discovered, primarily through immunological approaches (NPL 1: Boon T, Int J Cancer 1993 May 8, 54(2): 177-80; NPL 2: Boon T & van der Bruggen P, J Exp Med 1996 Mar. 1, 183(3): 725-9). Some of the TAAs are now currently undergoing clinical development as immunotherapeutic targets.
Identification of new TAAs, capable of inducing potent and specific anti-tumor immune responses, warrants further development and clinical application of peptide vaccination strategies for various types of cancer (NPL 3: Harris C C, J Natl Cancer Inst 1996 Oct. 16, 88(20): 1442-55; NPL 4: Butterfield L H et al., Cancer Res 1999 Jul. 1, 59(13): 3134-42; NPL 5: Vissers J L et al., Cancer Res 1999 Nov. 1, 59(21): 5554-9; NPL 6: van der Burg S H et al., J Immunol 1996 May 1, 156(9): 3308-14; NPL 7: Tanaka F et al., Cancer Res 1997 Oct. 15, 57(20): 4465-8; NPL 8: Fujie T et al., Int J Cancer 1999 Jan. 18, 80(2): 169-72; NPL 9: Kikuchi M et al., Int J Cancer 1999 May 5, 81(3): 459-66; NPL 10: Oiso M et al., Int J Cancer 1999 May 5, 81(3): 387-94). To date, there have been several reports of clinical trials using these tumor-associated antigen derived peptides. Unfortunately, only a low objective response rate has been observed in these cancer vaccine trials so far (NPL 11: Belli F et al., J Clin Oncol 2002 Oct. 15, 20(20): 4169-80; NPL 12: Coulie P G et al., Immunol Rev 2002 October, 188: 33-42; NPL 13: Rosenberg S A et al., Nat Med 2004 September, 10(9): 909-15).
Recently, HLA class I-binding peptide sequence can be expected using algorithms (NPL 14: Journal of Immunological Methods, (1995), Vol. 185, pp. 181-190, NPL 15: J. Immunol., (1994), Vol. 152, pp. 163-175, NPL 16: protein science, (2000), Vol. 9, pp. 1838-1846). However, it is hard to say that the expected epitope peptide can be processed naturally in the target cells and expressed on the target cell surface with HLA molecule. Moreover, the algorithm, for example BIMAS (http://bimas.dcrt.nih.gov/cgi-bin/molbio/ken_parker_comboform) (NPL 17: Parker K C, et al., (1994) J. Immunol.; 152(1):163-75; NPL 18: Kuzushima K, et al., (2001) Blood; 98(6):1872-81.)) can suggest the HLA molecule-binding peptide, but the suggested peptide is not so rigorous (NPL 19: Bachinsky M M, et. al., Cancer Immun. 2005 Mar. 22; 5:6.). Thus TAA screening still remains a lot of challenges and difficulties.
Pancreatic cancer has a poor prognosis, with an overall 5-year survival rate of about 5% (1). A surgical resection remains the only option for a long term survival, but patients with resectable pancreatic cancer are in the minority (9-22%) (NPL 20: Sener S F, et al. J Am Coll Surg 1999; 189:1-7, NPL 21: Eloubeidi M A, et al. Am J Surg 2006; 192:322-9, NPL 22: Goonetilleke K S, et al. Int J Surg 2007; 5:147-51.). Even in these patients, however, the 5-year survival rate remains approximately 20% in spite of surgery with a curative intent (NPL 23: Smeenk H G, et al. Langenbecks Arch Surg 2005; 390:94-103, NPL 24: Yeo C J, et al. Ann Surg 1995; 221:721-31.). Up to 80% of patients present with locally advanced or metastatic disease, and their median survival ranges from 6 to 9 months (NPL 25: Lockhart A C, et al. Gastroenterology 2005; 128:1642-54.). Hence, the development of novel therapeutic modalities is an issue of great importance, and immunotherapy may be a potential treatment for pancreatic cancer.
RAB6KIFL (KIF20A) was first identified to play a role in the dynamics of the Golgi apparatus through direct interaction with Rab6 small GTPase (NPL 26: Echard A, et al. Science 1998; 279:580-5.). RAB6KIFL belongs to the kinesin superfamily of motor proteins, which have critical functions in trafficking of molecules and organelles (NPL 26: Echard A, et al. Science 1998; 279:580-5, NPL 27: Hirokawa N, et al. Curr Opin Cell Biol 1998; 10:60-73, NPL 28: Allan V J, and Schroer T A. Curr Opin Cell Biol 1999; 11:476-82.). Recently, Taniuchi K et al. reported that RAB6KIFL was overexpressed in pancreatic cancer tissues (NPL 29: Taniuchi K, et al. Cancer Res 2005; 65:105-12.). They found evidence for a critical role of RAB6KIFL in pancreatic carcinogenesis.
Through gene expression profile analysis using a genome-wide cDNA microarray containing 23,040 genes, RAB6KIFL (KIF20A) was recently shown to be up-regulated in several cancers such as bladder cancer (PTL 1: WO2006/085684), small cell lung cancer (SCLC) (PTL 2: WO2007/013665) and hormone-refractory prostate cancer (HRPC) (PTL 3: WO2008/102906), the disclosures of which are incorporated by reference herein. Further, some epitope peptides of KIF20A gene products were also identified (PTL 4: WO2008/102557).